Interspecies Bombolitins Exhibit Structural Diversity upon Membrane Binding, Leading to Cell Specificity.
Interspecies Bombolitins Exhibit Structural Diversity upon Membrane Binding, Leading to Cell Specificity.
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DOI：
10.1016/j.bpj.2019.02.005
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发表时间：
2019-03
影响因子：
3.4
通讯作者：
Matthew G Roberson;Devin K. Smith;S. White;I. Wallace;M. J. Tucker
中科院分区：
文献类型：
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作者：
Matthew G Roberson;Devin K. Smith;S. White;I. Wallace;M. J. Tucker
熊蜂毒素是熊蜂属蜜蜂产生的一类肽，靶向并破坏细胞膜，导致裂解。抗微生物肽表现出由肽结构、脂质组成和细胞靶膜选择性之间的相互作用引起的各种作用机制。在本文中，显示显着的氨基酸序列相似性，BII和BL 6，bombolitins的抗微生物活性以及相关的十二烷基磷酸胆碱（DPC）胶束结合和膜诱导的肽构象变化进行了评估。红外光谱和圆二色光谱被用来评估每个bombolitin的结构-功能关系，结果表明，BII形成一个刚性和螺旋有序的二级结构后，结合到DPC胶束，而BL 6在很大程度上缺乏二级结构的顺序。此外，测定了每种肽对DPC胶束的结合亲和力，揭示了BL 6显示出超过两个数量级的结合亲和力差异。进一步研究了两种铃蟾毒素对大肠杆菌和酿酒酵母的生长抑制活性。有趣的是，BII特异性靶向酿酒酵母，而BL 6更有效地抑制大肠杆菌的共生生长。总体而言，BII和BL 6的抗微生物选择性和特异性在很大程度上取决于肽的一级和二级结构含量以及膜组成。
Bombolitins, a class of peptides produced by bees of the genusBombus, target and disrupt cellular membranes, leading to lysis. Antimicrobial peptides exhibit various mechanisms of action resulting from the interplay between peptide structure, lipid composition, and cellular target membrane selectivity. Herein, two bombolitins displaying significant amino-acid-sequence similarity, BII and BL6, were assessed for antimicrobial activity as well as correlated dodecylphosphocholine (DPC) micelle binding and membrane-induced peptide conformational changes. Infrared and circular dichroism spectroscopies were used to assess the structure-function relationship of each bombolitin, and the results indicate that BII forms a rigid and helically ordered secondary structure upon binding to DPC micelles, whereas BL6 largely lacks secondary structural order. Moreover, the binding affinity of each peptide to DPC micelles was determined, revealing that BL6 displayed a difference in binding affinity by over two orders of magnitude. Further investigations into the growth-inhibitory activity of the two bombolitins were performed againstEscherichia coliandSaccharomyces cerevisiae. Interestingly, BII specifically targetedS. cerevisiae, whereas BL6 more effectively inhibitedE. coligrowth. Overall, the antimicrobial selectivity and specificity of BII and BL6 are largely dependent on the primary as well as secondary structural content of the peptides and the membrane composition.